Back to results
US 10,385,071 B2Granted
Methods of preparing cytotoxic benzodiazepine derivatives
AssigneeImmunoGen, Inc.
InventorsBaudouin Gérard, Richard A. Silva, Michael Louis Miller, Manami Shizuka
Life of this patent
Estimating the term…
Abstract
The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.
Claims19
A method of preparing a compound of formula (A):
- or a salt thereof, comprising reacting a compound of formula (V):
- or a salt thereof, with a compound of formula (X):
- wherein:
- each double line between N and C independently represents a single bond or a double bond, provided that when it is a double bond X is absent and Y is —H, and when it is a single bond, X and Y are both —H;
- and
- E is —OH, halide or —C(═O)E is an activated ester.
3 more elements
A method of preparing a compound of formula (Xa):
- or a salt thereof, comprising the steps of:
- 1) reacting a compound of formula (VIII):
- or a salt thereof, with a compound of formula (c):
- or a salt thereof, to form a compound of formula (IX):
- or a salt thereof;
- and
- 2) reacting the compound of formula (IX) with a carboxylic acid deprotecting agent to form the compound of formula (Xa) or a salt thereof, wherein E1 is —OH, halide or —C(═O)E1 is an activated ester;
- and P1 is a carboxylic acid protecting group.
5 more elements
A method of preparing a compound of formula (II),
- comprising reacting a compound of formula (I):
- with hydrochloric acid in toluene.
A method of preparing a compound of formula (IV-1):
- or a salt thereof, comprising the steps of:
- 1) reacting a compound of formula (I):
- with hydrochloric acid in toluene to form a compound of formula (II):
- 2) reacting the compound of formula (II) with a monomer compound of formula (a),
- to form a compound of formula (III):
- or a salt thereof;
- 3) reacting the compound of formula (III) or a salt thereof with a monomer compound of formula (b):
- to form the compound of formula (IV-1) or a salt thereof.
5 more elements
A method of preparing a compound of formula (A-1)
- or salt thereof, comprising the steps of:
- 1) reacting a compound of formula (I):
- with hydrochloric acid in toluene to form a compound of formula (II):
- 2) reacting the compound of formula (II) with a monomer compound of formula (a),
- to form a compound of formula (III):
- or a salt thereof;
- 3) reacting the compound of formula (III) or a salt thereof with a monomer compound of formula (b):
- to form a compound of formula (IV-1):
- or a salt thereof;
- 4) reacting the compound of formula (IV-1) or a salt thereof with a reducing agent to form a compound of formula (V-1):
- or a salt thereof;
- and
- 5) reacting the compound of formula (V-1) or a salt thereof, with a compound of formula (X-1):
- to form the compound of formula (A-1),
- or a salt thereof, wherein E is —OH, halide or —C(═O)E is an activated ester.
12 more elements
Dependencies are inferred from the claim text.